68Ga-FAPI PET/CT Depicted the Fibrosis of Ischemic Colitis.

ABSTRACT: Ischemic colitis is the most common form of ischemic bowel disease; identification of ischemic colitis with PET/CT is rare. We present a case of unexplained ischemic colitis in a 66-year-old man who underwent 18F-FDG PET/CT to exclude intestinal malignancy and was subsequently recruited in a clinical trial regarding 68Ga-FAPI. 18F-FDG PET/CT showed intense activity in the intestinal lumen where mucosa had chronic inflammation. Conversely, 68Ga-FAPI PET/CT revealed high tracer uptake in the intestinal wall and adjacent mesentery. Our case showed the different distribution pattern of 18F-FDG and 68Ga-FAPI in ischemic colitis.

68 Ga-DOTATATE PET/CT Detected Bone Metastasis Earlier Than 68 Ga-FAPI PET/CT and 99m Tc-MDP Bone Scintigraphy in a Patient With Nasopharyngeal Carcinoma.

ABSTRACT: A 53-year-old man with newly diagnosed nasopharyngeal carcinoma (NPC) underwent 99m Tc-MDP bone scintigraphy for the potential bone metastases, and paired 68 Ga-DOTATATE and 68 Ga-FAPI PET/CT for initial staging. 68 Ga-DOTATATE PET/CT identified 2 abnormal foci with increased tracer uptake in the cervical vertebra and the ilium, whereas 68 Ga-FAPI PET/CT and bone scan detected only the ilium lesion. A subsequent biopsy confirmed NPC metastasis in the ilium. Furthermore, baseline and follow-up bone scintigraphy revealed that the positive lesion in the cervical vertebra, as indicated in 68 Ga-DOTATATE PET/CT, was also a bone metastasis. This case highlighted the potential superiority of 68 Ga-DOTATATE in NPC.

A head-to-head comparison of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in patients with nasopharyngeal carcinoma: a single-center, prospective study.

PURPOSE: We aimed to compare the staging efficiency of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in nasopharyngeal carcinoma (NPC) patients. METHODS: Thirty-nine patients with pathologically confirmed NPC were enrolled in this prospective study. Each patient underwent paired [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT on 2 successive days. The accuracy of two PET/CT for assessing T, N, and M stages was compared by using head-and-neck MRI, histopathologic diagnosis and follow-up results as reference standards. The radiotracer uptake derived from two PETs was also compared. RESULTS: For treatment-naïve patients, [68Ga]Ga-DOTATATE PET/CT showed identical sensitivity for the primary tumours but clearer tumor delineation induced by higher tumour-to-background (TBR) ratio (19.1 ± 8.7 vs. 12.4 ± 7.7, P = 0.003), compared with [68Ga]Ga-FAPI PET/CT. Regarding cervical lymph node (CLN) metastases, [68Ga]Ga-DOTATATE PET had significantly better sensitivity and accuracy based on neck sides (98% vs. 82%, P < 0.001; 99% vs. 88% P = 0.008), neck levels (98% vs. 78%, 99% vs. 97%; both P < 0.001) and individual nodes (89% vs. 56%, 91% vs. 76%; both P < 0.001), and higher TBR (8.1 ± 4.1 vs. 6.3 ± 3.7, P < 0.001). Additionally, [68Ga]Ga-DOTATATE PET/CT revealed higher sensitivity and accuracy for distant metastases (96% vs. 53%, 95% vs. 52%; both P < 0.001), particularly in bone metastases (99% vs. 49%, 97% vs. 49%; both P < 0.001). For post-treatment patients, [68Ga]Ga-DOTATATE PET/CT identified one more true-negative case than [68Ga]Ga-FAPI PET/CT. CONCLUSION: [68Ga]Ga-DOTATATE PET/CT performed better than [68Ga]Ga-FAPI PET/CT in visualizing the primary tumours, detecting the metastatic lesions and identifying the local recurrence, suggesting [68Ga]Ga-DOTATATE PET/CT may be superior to [68Ga]Ga-FAPI PET/CT for NPC staging.

Corrigendum: Epigenetic-mediated downregulation of zinc finger protein 671 (ZNF671) predicts poor prognosis in multiple solid tumors.

[This corrects the article DOI: 10.3389/fonc.2019.00342.].

Clinical value of [18F]F-FDG PET/CT in patients with suspected paraneoplastic dermatoses: Diagnostic performance and impact on clinical management.

PURPOSE: We retrospectively evaluate the diagnostic performance of 2-deoxy-2[18F]fuoro-D-glucose([18F]F-FDG) PET/CT and its impact on clinical management in patients with suspected paraneoplastic dermatoses (PD). MATERIALS AND METHODS: From an institutional PET/CT database (2014-2022), we retrospectively analyzed patients who were clinically suspected with PD and underwent [18F]F-FDG PET/CT for screening an underlying malignancy. For all scans, positive mucocutaneous lesions and PET-indicated malignancies were assessed, and the degree of FDG avidity among different dermatoses were quantified. The final diagnoses of dermatoses and neoplasms were based on pathologic results, international diagnostic standard and follow-up. We assessed the recommended and applied therapies before and after [18F]F-FDG PET/CT and noted whether the patient management changed on the basis of the [18F]F-FDG PET/CT results. RESULTS: We analyzed 60 patients with 10 types of dermatoses in this study. Finally, 19 of the 60 patients who had both of specific dermatosis and contemporaneous neoplasm were diagnosed with PD. [18F]F-FDG PET could identify the underlying neoplasms in 18/19 (94.7%) PD patients, and led to a change of the management in 9/19 (47.4%) PD patients. In addition, the mucocutaneous manifestations of [18F]F-FDG PET/CT associated with several specific dermatoses were characteristic. CONCLUSIONS: This study highlighted the value of [18F]F-FDG PET/CT as a useful tool for evaluation of patients with suspected PD to unveil the underlying culprit tumor, and profoundly supports the clinical management of PD patients.

Overexpression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation.

PURPOSE: POU3F2 is associated with malignant behaviors and poor prognosis in cancer. However, the function and mechanism of POU3F2 in breast cancer remain to be elucidated. Our study aimed to explore the role of POU3F2 in triple-negative breast cancer and radiotherapy. METHODS: POU3F2 expression was examined by RT-PCR and Western blot. The proliferation of cancer cells was measured by MTT assay. Migration of cancer cells was determined by Transwell assay and wound healing assay. To determine which protein interacts with POU3F2, Co-IP was performed. Survival analysis was performed based on the online database GEPIA. DNA damage after radiation was examined by Comet Assay. Radiosensitivity was evaluated with clonogenic survival assays. A tumor xenograft model was established with MDA-MB-231 breast cancer cells in BALB/c nude mice to explore the effect of POU3F2 in vivo. RESULTS: We found that the expression of POU3F2 was significantly elevated in breast cancer cells, especially in TNBC, and higher POU3F2 expression was related to poor prognosis of patients with breast cancer. Functional assays revealed that POU3F2 promoted proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells in vitro and in vivo. In addition, the knockdown of POU3F2 decreased the radioresistance of TNBC cells in vitro. Furthermore, POU3F2 could enhance the activation of the Akt pathway by interacting with ARNT2, thereby promoting proliferation and radioresistance in TNBC cells. CONCLUSIONS: Our results provide evidence that high expression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation by interacting with ARNT2.

[68Ga]Ga-FAPI PET/CT Improves the T Staging of Patients with Newly Diagnosed Nasopharyngeal Carcinoma: A Comparison with [18F]F-FDG.

PURPOSE: This study aimed to explore the value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in the initial staging of patients with newly diagnosed nasopharyngeal carcinoma (NPC), compared with 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) PET/CT. MATERIALS AND METHODS: Forty-seven treatment-naïve patients with newly diagnosed NPC underwent magnetic resonance imaging (MRI), [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT within 1 week. The diagnostic efficiency of all imaging modalities for evaluating primary tumour extension was compared from the two aspects of soft tissue and bony structure involvement. The accuracy of two PET/CT methods for diagnosing cervical lymph node (CLN) metastases was compared, and MRI served as the standard reference. T and N stages were assessed by MRI, [68Ga]Ga-FAPI PET/CT and [18F]F-FDG PET/CT. Immunohistochemical (IHC) staining for FAP was conducted in 22 of the patients. RESULTS: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in the assessment of primary tumour invasion in the cavernous sinus (10 vs. 1, p < 0.001) and bony structures (207 vs. 177, p < 0.001). Compared with MRI, [68Ga]Ga-FAPI PET/CT upgraded and underestimated T stage in 13 and 2 patients, while [18F]F-FDG PET/CT upgraded and underestimated T stage in 5 and 13 patients. However, [68Ga]Ga-FAPI PET/CT was inferior to [18F]F-FDG PET/CT in diagnosing positive CLNs based on the analyses of patients, neck sides, neck levels and individual nodes. [68Ga]Ga-FAPI PET/CT changed therapeutic schedules in 8 patients because of stage group changes. The presence of FAP with high quantity and intensity in cancer-associated fibroblasts (CAFs) was confirmed in all tumour specimens. CONCLUSION: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in detecting the cavernous sinus and bony structure involvement of primary NPC tumours, suggesting its value in improving T staging and therapeutic regimen selection. However, the performance of [68Ga]Ga-FAPI PET/CT is less promising for N staging because it detected fewer positive CLNs than [18F]F-FDG PET/CT.

68Ga-FAPI and 18F-PET/CT Images in Intestinal Tuberculosis.

ABSTRACT: A 28-year-old woman presented with abdominal pain, bowel dysfunction, and weight loss for 3 months. 18F-FDG PET/CT revealed multiple hypermetabolic lesions in the intestines and peritoneal thickening/caking with moderate FDG activity. 68Ga-FAPI PET/CT showed intense FAPI uptake in the aforementioned FDG-avid lesions and a larger number of abnormal foci with intense FAPI uptake in the peritoneum than that shown in 18F-FDG images. Endoscopy-guided biopsy from the colonic mucosa was consistent with tuberculosis. The positive findings of 68Ga-FAPI in the current case highlighted that 68Ga-FAPI may have value in the evaluation of intestinal tuberculosis.

Characterization of the benign lesions with increased 68Ga-FAPI-04 uptake in PET/CT.

OBJECTIVES: The objective of the study was to characterize benign lesions showing increased 68Ga-FAPI-04 uptake on FAPI PET/CT. METHODS: We retrospectively reviewed 182 patients with suspected various cancers who were performed 68Ga-FAPI-04 PET/CT imaging from August 2020 to December 2020. The diagnoses of the benign lesions were made by the CT findings (CT), other imaging information (OII) (contrast enhance CT, FDG PET, ultrasound, MRI or others), clinical information (CI) (medical history, laboratory examination, symptom, physical sign and follow-up information) or histological biopsy (HB). RESULTS: A total of 185 primary malignant tumors were detected by FAPI PET/CT with the median SUVmax of 9.0 (range from 0.97 to 25.71). There were 360 benign lesions with increased FAPI uptake were detected in 146 (146/182, 80.2%) patients with the median SUVmax of 3.64 (range from 1.39 to 21.56), including inflammatory processes (n = 231, 64.2%), exostosis (n = 54, 15%), hemorrhoid (n = 47, 13.1%), fracture (n = 17, 4.7%), hepatic fibrosis (n = 4, 1.1%), and others (n = 7, 1.9%). CONCLUSION: Benign lesions with increased 68Ga-FAPI-04 uptake are common. The overall SUVmax of benign lesions is lower than that of malignant tumors, however there is a large overlap of SUVmax range. Similar to FDG PET, some benign lesions can be easily diagnosed by combining CT findings, special location and clinical data, but there are still some lesions that may be confused with malignant lesions, which need to be paid more attention. TRAIL REGISTRATION: NIH ClinicalTrials.gov (NCT04499365).

Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells.

Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.

Widespread Skin Infiltration of Leukemia Cutis on 18F-FDG PET/CT.

A 67-year-old man experienced multiple cutaneous nodules for 3 weeks. His initial skin biopsy only showed local inflammation. However, after a 2-week anti-inflammation therapy, the skin manifestations were not improved while the leukocyte count gradually increased. FDG PET/CT revealed widespread cutaneous and subcutaneous hypermetabolic lesions in many parts of the body, and heterogeneously increased uptakes in the bone marrow. Bone marrow biopsy and second skin biopsy were performed. Pathological examination from both specimen demonstrated acute monocytic leukemia.

Corrigendum: The Tumor Suppressor Role of Zinc Finger Protein 671 (ZNF671) in Multiple Tumors Based on Cancer Single-Cell Sequencing.

[This corrects the article DOI: 10.3389/fonc.2019.01214.].

Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma.

Radiotherapy and adjuvant cisplatin (DDP) chemotherapy are standard administrations applied to treat nasopharyngeal carcinoma (NPC). However, the molecular changes and functions of DDP in NPC chemo-resistance remain poorly understood. In the present study, transcriptomic sequencing between 5-8F and 5-8F/DDP cells was performed to identify differential expression and alternative splicing (AS) characteristics in DDP-resistant NPC cells. Transcriptomic profiling identified 1,757 upregulated genes and 1,473 downregulated differentially expressed genes (DEGs). Bioinformatic analysis revealed that these DEGs were associated with or participated in important biological regulatory functions in NPC. Validation of 20 significant DEGs using quantitative real-time reverse transcription PCR showed that the expression patterns of 17 mRNAs were in accordance with the sequencing data. Intron retention was identified as the major AS event in chemoresistant cells. Furthermore, the expression level of matrix metalloproteinase 1 (MMP1), which was one of the most upregulated mRNAs in the chemoresistant cell lines, was significantly associated with the migration, invasion, and proliferation of NPC cells in vitro. Our study revealed that dysregulated genes and AS-mediated DDP chemoresistance might play important roles in NPC development and progression. Targeting aberrantly expressed genes might clarify the pathogenesis of NPC and contribute to developing new therapeutic strategies for NPC.

The Tumor Suppressor Role of Zinc Finger Protein 671 (ZNF671) in Multiple Tumors Based on Cancer Single-Cell Sequencing.

In humans, zinc finger protein 671 (ZNF671) is a type of transcription factor. However, the contribution of tumor heterogeneity to the functional role of ZNF671 remains unknown. The present study aimed to determine the functional states of ZNF671 in cancer single cells based on single-cell sequencing datasets (scRNA-seq). We collected cancer-related ZNF671 scRNA-seq datasets and analyzed ZNF671 in the datasets. We evaluated 14 functional states of ZNF671 in cancers and performed ZNF671 expression and function state correlation analysis. We further applied t-distributed stochastic neighbor embedding to describe the distribution of cancer cells and to explore the functional state of ZNF671 in cancer subgroups. We found that ZNF671 was downregulated in eight cancer-related ZNF671 scRNA-seq datasets. Functional analysis identified that ZNF671 might play a tumor suppressor role in cancer. The heterogeneous functional states of cell subgroups and correlation analysis showed that ZNF671 played tumor suppressor roles in heterogeneous cancer cell populations. Western blot and transwell assays identified that ZNF671 inhibited EMT, migration, and invasion of CNS cancers, lung cancer, melanoma, and breast carcinoma in vitro. These results from cancer single-cell sequencing indicated that ZNF671 played a tumor suppressor role in multiple tumors and may provide us with new insights into the role of ZNF671 for cancer treatment.

Long noncoding RNA LINC02582 acts downstream of miR-200c to promote radioresistance through CHK1 in breast cancer cells.

Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.

Epigenetic-Mediated Downregulation of Zinc Finger Protein 671 (ZNF671) Predicts Poor Prognosis in Multiple Solid Tumors.

Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. However, the methylation status, expression, and prognostic role of ZNF671 in solid tumors remain unclear. The aim of this study was to explore the relationship between ZNF671 and the prognosis of patients with solid tumors. We performed a pan-cancer analysis of the methylation status and mRNA and protein expression of ZNF671 using The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas. We further evaluated the prognostic value of ZNF671 expression among numerous cancer types using the "Kaplan-Meier plotter" (KM plotter) database. We found that downregulation of ZNF671 is associated with hypermethylation of its promoter. Survival analysis established that the downregulation of ZNF671 predicts poor prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and uterine corpus endometrial carcinoma (UCEC) solid tumors. CCK-8 and Transwell functional assays showed that ZNF671 could inhibit tumor cell proliferation, migration, and invasion. These results indicate that ZNF671 is an excellent predictive factor for BRCA, CESC, HNSC, KIRP, LUAD, PAAD, SARC, and UCEC solid tumors and may play crucial roles in the development and progression of these tumors.